Brain microbleeds (BMB) are associated with ischemic and hemorrhagic stroke, cerebral amyloid angiopathy (CAA), neurotrauma, Alzheimer's disease (AD), vascular dementia, cognitive decline, hypertension and aging. The presence of BMB in ischemic stroke, intracerebral hemorrhage (ICH) and CAA is associated with future hemorrhage. Whether presence of BMB increases the risk of bleeding when thrombolytic and antithrombotic agents are used is an important and controversial question. Thus, BMB are associated with both chronic and acute illness of no small consequence in our aging population.
BMB are visible in gradient recalled echo (GRE) T2* magnetic resonance (MR) imaging as focal regions of signal loss and have been histopathologically related to hemosiderin, the (paramagnetic) iron-protein complex associated with pathologic iron storage following hemorrhage and ferritin breakdown. Thus, BMB represent a source of pathologic iron in the brain that is potentially cytotoxic (e.g., by free radical production through the Fenton reaction). Oxidative damage, iron accumulation and/or changes in iron metabolism have been implicated in neurodegenerative and cerebrovascular diseases. In addition, since iron is deposited at the site of a BMB in proportion to the amount of extravasated blood, iron content in BMB can be considered a marker for the severity of underlying vessel disease. Therefore the quantified iron content in BMB is potentially informative regarding disease progression and the efficacy of treatment.
Past efforts to quantify brain iron have focused on content estimation within distributed brain regions. BMB, however, represent a localized source of iron deposition. Iron content and concentration of BMB have been heretofore absent in the literature. In addition, conventional “magnitude” MR images have significant limitations especially for localized iron quantification, and the well known blooming effect typically obscures the true dimensions of an iron susceptibility source. A few studies have compared radiologic BMB to postmortem human tissue and have noted evidence of associated tissue damage. However, in vivo methods would allow the investigation of temporal relationships regarding tissue damage evolution following BMB and possible interventions. In particular, methods correlating BMB iron content levels with the severity and evolution of tissue damage can shed light on the role of iron in the disease process.
Therefore, there is the need for an improved method of quantifying iron in BMB, which is capable of determining iron content and/or concentration, that is not associated with disadvantages, like the blooming effect, of conventional “magnitude” MR images.